Author information

¹Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

²Peking University 302 Clinical Medical School, Beijing, China.

³Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China.

⁴Department of Hepatobiliary Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.

⁵Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

⁶Department of Liver Diseases, the 960th Hospital of Chinese PLA Joint Logistics Support Force, Jinan, Shandong Province, China.

⁷Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou, University, Zhengzhou, Henan Province, China.

⁸Department of Liver Disease, Fuyang 2nd People's Hospital, Fuyang, Anhui Province, China.

⁹Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China.

¹⁰Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China.

¹¹Department of Infectious Diseases, Southwest Hospital, Army Military Medical University, Chongqing, China.

¹²Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China.

¹³Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China.

¹⁴Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China.

¹⁵National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.

Abstract

Background and aims: The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes.

Approach and results: In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation).

Conclusions: The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.